Neoadjuvant of Sintilimab Combined Weekly Metronomic Chemotherapy (PLOF) for Resectable Locally Advanced Gastric Cancer

NCT ID: NCT06054906

Last Updated: 2024-12-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-18
• Study Completion Date: 2025-12-31

Brief Summary

To evaluate efficacy and safety of Neoadjuvant of Sintilimab Combined Weekly Metronomic Chemotherapy (PLOF) in resectable locally advanced gastric cancer.

Detailed Description

This is a single-arm clinical study to enroll 50 patients with gastric cancer (cTNM diagnosis of cT3-4aN1-3M0). Each enrolled patient will be assigned a case number. Both this case number and the patient's initials will be entered on each page of the case report form.

Enrolled patients receive a neoadjuvant regimen of POLF in combination with sindilizumab: preoperatively, they receive a POLF regimen (paclitaxel 60 mg/m2, oxaliplatin 50 mg/m2, and 5-fluorouracil 425 mg/m2) administered once weekly for a total of 6 doses, and in combination with sindilizumab 200 mg intravenously once every 3 weeks for a total of 2 doses. Upon completion of the evaluation, patients whose tumors were judged to be resectable underwent radical surgery and received six postoperative doses of the POLF regimen and two doses of Sindilizumab as adjuvant therapy.

Postoperative imaging evaluations will be performed every three months until disease recurrence. Survival follow-up was performed every three months after disease recurrence. Patients will receive neoadjuvant therapy for 6 weeks preoperatively and adjuvant therapy for 6 weeks postoperatively unless intolerable toxicity occurs, the patient refuses to continue treatment, or treatment is delayed beyond 3 weeks. Patients will be under study observation during treatment and 30 days after treatment termination, and will receive long-term follow-up for 5 years postoperatively. Ultimately, pCR and MPR will be the primary study endpoints, and ORR, DCR, 2-year PFS rate, 3-year OS rate and safety will be the secondary study endpoints to evaluate the efficacy and safety of the neoadjuvant regimen of POLF combined with sindilizumab, as well as to explore the immune activation effect and mechanism of the regimen using peripheral blood and tumor tissue samples.

Conditions

Gastric Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

sintilimab+metronomic PLOF

sintilimab therapy(200mg, iv,d1,Q3W, 2cycles)and PLOF chemotherapy (Paclitaxel 60 mg/m2, oxaliplatin 50 mg/m2, 5-fluorouracil 425mg/m2, d1, QW, 6cycles) followed by adjuvant sintilimab therapy(200mg, iv,d1,Q3W, 2cycles)and PLOF chemotherapy (Paclitaxel 60 mg/m2, oxaliplatin 50 mg/m2, 5-fluorouracil 425mg/m2, d1, QW, 6cycles) neoadjuvant chemotherapy (8 weeks) preceding surgery (3 weeks after completion of chemotherapy) followed by adjuvant chemotherapy (16 weeks, begin within 12 weeks after surgery)

Group Type: EXPERIMENTAL

sintilimab+metronomic PLOF

Intervention Type: DRUG

Drug: Sintilimab 200mg iv d1 Q3W, 2cycles

Drug: Paclitaxel 60 mg/m2, d1, QW,6cycles

Drug: Oxaliplatin 50 mg/m2, d1, QW, 6cycles

Drug: 5-fluorouracil 425mg/m2 ,d1 ,QW, 6cycles

Interventions

sintilimab+metronomic PLOF

Drug: Sintilimab 200mg iv d1 Q3W, 2cycles

Drug: Paclitaxel 60 mg/m2, d1, QW,6cycles

Drug: Oxaliplatin 50 mg/m2, d1, QW, 6cycles

Drug: 5-fluorouracil 425mg/m2 ,d1 ,QW, 6cycles

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Signed written Informed Consent Form

2. Male or female, age ≥ 18 years old

3. Histologically confirmed gastric adenocarcinoma, diagnosed as locally progressive according to the AJCC 8th ed, cTNM diagnosis of cT3-4aN1-3M0 and resectable lesion as assessed by the investigator

4. No prior systemic therapy such as surgery, radiotherapy, or immunotherapy for the disease at hand

5. Consent to radical surgical treatment and no contraindications to surgery as determined by the surgeon

6. ECOG PS: 0-1 score

7. Expected survival > 6 months

8. Adequate organ function, must meet the following laboratory specifications:

8.1 Absolute neutrophil count (ANC) ≥ 1.0x10^9/L; 8.2 Platelets ≥ 80x10^9/L; 8.3 Hemoglobin > 7g/dL; 8.4 Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (Total bilirubin > 1.5 x ULN but direct bilirubin ≤ ULN are allowed to be enrolled); 8.5 AST, ALT ≤ 2.5×ULN; 8.6 Blood creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 60 ml/min; 8.7 INR or PT ≤ 1.5 times ULN; 8.8 TSH within normal range (Enrollment allowed if baseline TSH is outside normal range but FT4 is within normal range); 8.9 Myocardial enzyme profile within normal range;

9. Negative pregnancy test in women of childbearing age

10. Need to use contraception with an annual failure rate of less than 1% if there is a risk of conception

Exclusion Criteria

1. Endoscopically show signs of active bleeding from the lesion

2. Current participation in an interventional clinical study or treatment with another investigational drug or use of an investigational device within 4 weeks prior to the first dose of study drug

3. Prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents, or agents targeting CTLA-4, OX-40, CD137, etc.

4. Diagnosis of a malignant disease other than gastric cancer within 5 years prior to the first dose of therapy

5. Active autoimmune disease requiring systemic therapy within 2 years prior to the first dose of the drug

6. Live vaccination within 30 days prior to the first administration of the drug

7. Have received systemic systemic therapy with proprietary Chinese medicines with antitumor indications or immunomodulatory drugs within 2 weeks prior to the first administration of the drug

8. Have received systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of treatment

9. Has not fully recovered from any intervention-induced toxicity and/or complications (excluding malaise or alopecia) prior to initiation of therapy

10. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation

11. Known hypersensitivity to drugs used in this study

12. Known history of HIV infection

13. Untreated active hepatitis B

14. Active HCV infection

15. Pregnant or lactating women

16. The presence of any serious or uncontrolled systemic disease

17. Other factors that, in the judgment of the investigator, may affect the outcome of the study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Huashan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Zhongguang Luo, MD

Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Huashan Hospital, Fudan University

Shanghai, , China

Site Status: RECRUITING

Countries

China

Facility Contacts

Wanwei Zheng

Role: primary

Other Identifiers

KY2022-1018

Identifier Type: -

Identifier Source: org_study_id